文摘
Pursuing our earlier efforts in the himbacine-based thrombin receptor antagonist area, we have synthesizeda series of compounds that incorporate heteroatoms in the C-ring of the tricyclic motif. This effort hasresulted in the identification of several potent heterocyclic analogs with excellent affinity for the thrombinreceptor. Several of these compounds demonstrated robust inhibition of platelet aggregation in an ex vivomodel in cynomolgus monkeys following oral administration. A detailed profile of 28b, a benchmarkcompound in this series, with a Ki of 4.3 nM, is presented.